Population pharmacokinetic analysis of entrectinib in pediatric and adult patients with advanced/metastatic solid tumors: support of new drug application submission
ConclusionsA robust population PK model was built and qualified for entrectinib and M5, describing linear PK for both entities. This model was used to support the ROZLYTREK® new drug application. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - September 18, 2021 Category: Cancer & Oncology Source Type: research

Megestrol acetate is a specific inducer of CYP3A4 mediated by human pregnane X receptor
ConclusionThe results suggest that megestrol acetate is a specific inducer of CYP3A4 mediated by hPXR and therefore has the potential to cause drug interactions, especially in the co-administration with drugs that are substrates of CYP3A4. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - September 15, 2021 Category: Cancer & Oncology Source Type: research

Pretherapeutic screening for Dihydropyrimidine deshydrogenase deficiency in measuring uracilemia in dialysis patients leads to a high rate of falsely positive results
ConclusionPhenotyping based on measuring plasma [U] before a dialysis sessions in ESRD patients is associated with an unacceptable high rate of false positives. The optimal strategy for the identification of patients with DPD deficiency in this population would be the monitor the [UH2]:[U] ratio, which remains unaffected. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - September 13, 2021 Category: Cancer & Oncology Source Type: research

The related miRNAs involved in doxorubicin resistance or sensitivity of various cancers: an update
AbstractDoxorubicin (DOX) is an effective chemotherapy agent against a wide variety of tumors. However, intrinsic or acquired resistance diminishes the sensitivity of cancer cells to DOX, which leads to a cancer relapse and treatment failure. Resolutions to this challenge includes identification of the molecular pathways underlying DOX sensitivity/resistance and the development of innovative techniques to boost DOX sensitivity. DOX is classified as a Topoisomerase II poison, which is cytotoxic to rapidly dividing tumor cells. Molecular mechanisms responsible for DOX resistance include effective DNA repair and resumption of...
Source: Cancer Chemotherapy and Pharmacology - September 12, 2021 Category: Cancer & Oncology Source Type: research

Ruxolitinib exposure in patients with acute and chronic graft versus host disease in routine clinical practice —a prospective single-center trial
ConclusionRuxolitinib exposure is increased in GvHD patients in comparison to myelofibrosis patients due to reduced clearance and comedication with CYP3A4 or CYP2C9 inhibitors. Elevated Ruxolitinib trough concentrations might be a surrogate for toxicity. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - September 10, 2021 Category: Cancer & Oncology Source Type: research

Human placental extract ameliorates methotrexate-induced hepatotoxicity in rats via regulating antioxidative and anti-inflammatory responses
ConclusionHPE has the ability to ameliorate methotrexate-induced liver injury in rats by mechanisms that include boosting antioxidative responses and down-regulating MDA and pro-inflammatory cytokine production. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - September 10, 2021 Category: Cancer & Oncology Source Type: research

Impact of fedratinib on the pharmacokinetics of transporter probe substrates using a cocktail approach
ConclusionsThese results suggest that fedratinib has minimal impact on the exposure of P-gp, BCRP, OATP1B1/1B3, OCT2, and MATE1/2-K substrates. Since renal clearance of metformin was decreased in the presence of fedratinib, caution should be exercised in using coadministered drugs that are renally excreted via OCT2 and MATEs.Trial registrationClinicaltrials.gov NCT04231435 on January 18, 2020. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - September 3, 2021 Category: Cancer & Oncology Source Type: research

Zileuton inhibits arachidonate-5-lipoxygenase to exert antitumor effects in preclinical cervical cancer models
ConclusionsOur work demonstrates that the ALOX5-5-HETE axis is activated in cervical cancer, with important roles in growth and survival, and this can be therapeutically targeted by zileuton. Our findings also provide preclinical evidence to assess the efficacy of zileuton in cervical cancer in clinical settings. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - September 3, 2021 Category: Cancer & Oncology Source Type: research

Comment on “Pharmacodynamics of cerebrospinal fluid asparagine after asparaginase”
(Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - September 1, 2021 Category: Cancer & Oncology Source Type: research

Arginine depriving enzymes: applications as emerging therapeutics in cancer treatment
AbstractCancer is the second leading cause of death globally. Chemotherapy and radiation therapy and other medications are employed to treat various types of cancer. However, each treatment has its own set of side effects, owing to its low specificity. As a result, there is an urgent need for newer therapeutics that do not disrupt healthy cells ’ normal functioning. Depriving nutrient or non/semi-essential amino acids to which cancerous cells are auxotrophic remains one such promising anticancer strategy.l-Arginine (Arg) is a semi-essential vital amino acid involved in versatile metabolic processes, signaling pathways, a...
Source: Cancer Chemotherapy and Pharmacology - August 19, 2021 Category: Cancer & Oncology Source Type: research

Covariate effects and population pharmacokinetic analysis of the anti-FGFR2b antibody bemarituzumab in patients from phase 1 to phase 2 trials
ConclusionNo covariate had a clinically meaningful impact on bemarituzumab exposure. These results indicate that dose adjustment of bemarituzumab is not necessary, based on the aforementioned covariates, for a future phase 3 trial in gastric and gastroesophageal junction adenocarcinoma population with FGFR2b overexpression  in combination with mFOLFOX6. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - August 12, 2021 Category: Cancer & Oncology Source Type: research

A phase 1, open-label, drug –drug interaction study of rucaparib with rosuvastatin and oral contraceptives in patients with advanced solid tumors
ConclusionRucaparib 600  mg BID weakly increased the plasma exposure to rosuvastatin or oral contraceptives. Rucaparib safety profile when coadministered with rosuvastatin or oral contraceptives was consistent with that of rucaparib monotherapy. Dose adjustments of rosuvastatin and oral contraceptives are not necessary wh en coadministered with rucaparib.ClinicalTrials.gov NCT03954366;Date of registration May 17, 2019. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - August 9, 2021 Category: Cancer & Oncology Source Type: research

Minimal PK/PD model for simultaneous description of the maximal tolerated dose and metronomic treatment outcomes in mouse tumor models
ConclusionOur results demonstrate that the proposed model presents a minimal yet efficient tool for modeling outcomes in different treatment regimens in mice. We hope that this model has the potential for use in clinical practice in the development of patient-specific chemotherapy scheduling protocols based on observed treatment response. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - August 5, 2021 Category: Cancer & Oncology Source Type: research

Correction to: Anticancer potential of metformin: focusing on gastrointestinal cancers
(Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - August 2, 2021 Category: Cancer & Oncology Source Type: research

Cyclophosphamide bioactivation pharmacogenetics in breast cancer patients
ConclusionComedications may be the cause for this inter-occasion variation in bioactivation of cyclophosphamide and the ensuing phenoconversion may account for the conflicting reports in the literature about the relationship betweenCYP2C19 genotype and CP bioactivation pharmacokinetics. Trial registration ANZCTR363222 (6/11/2012, retrospectively registered). (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - July 27, 2021 Category: Cancer & Oncology Source Type: research